| Affiliation: | 1. Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237 China;2. Department of Chemical Sciences, University of Naples Federico II, Via Cintia 4, 80126 Napoli, Italy;3. Department of Chemical Sciences, University of Naples Federico II, Via Cintia 4, 80126 Napoli, Italy Department of Chemistry, School of Science, Osaka University, 1-1 Osaka University Machikaneyama, Toyonaka, Osaka, 560-0043 Japan;4. State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 China |
| Abstract: | Cyclodextrins are widely used as carriers of small molecules for drug delivery owing to their remarkable host properties and excellent biocompatibility. However, cyclic oligosaccharides with different sizes and shapes are limited. Cycloglycosylation of ultra-large bifunctional saccharide precursors is challenging due to the constrained conformational spaces. Herein we report a promoter-controlled cycloglycosylation approach for the synthesis of cyclic α-(1→6)-linked mannosides up to a 32-mer. Cycloglycosylation of the bifunctional thioglycosides and (Z)-ynenoates was found to be highly dependent on the promoters. In particular, a sufficient amount of a gold(I) complex played a key role in the proper preorganization of the ultra-large cyclic transition state, providing a cyclic 32-mer polymannoside, which represents the largest synthetic cyclic polysaccharide to date. NMR experiments and a computational study revealed that the cyclic 2-mer, 4-mer, 8-mer, 16-mer, and 32-mer mannosides adopted different conformational states and shapes. |
